Effect of Low Doses of Ketamine in Mitigating Cognitive Impairment Induced by Propofol Anesthesia in Rats

Misha Hou and Jiaping Zhao

Background and Objective: Propofol anesthesia induces certain neurotoxic effects, leading to apoptosis of hippocampal neurons during the developmental stage of the brain, thereby triggering postoperative cognitive dysfunction (POCD). Ketamine combined with propofol anesthesia is safer and promotes postoperative cognitive recovery, but the specific mechanism of action remains to be further elucidated. This study aims to elucidate the efficacy and underlying mechanism of low doses of ketamine in ameliorating cognitive impairment engendered by propofol anesthesia in a rat model. Materials and Methods: Thirty-two, 20-day-old SPF rats were randomly assigned to group C (100 mg/kg fat emulsion), group P (50 mg/kg propofol), group EP (10 mg/kg ketamine, 50 mg/kg propofol) and group LYEP (25 μg LY294002, followed by ketamine-propofol after 30 min), n = 8 each. The hippocampal neuronal apoptosis, expression of PI3K/Akt signaling pathway-related and synaptic plasticity-related proteins and pro- and anti-inflammatory factor levels were evaluated. Results: Compared to group P, groups EP and LYEP exhibited elevated P-Akt/Akt, IL-4, IL-10, GAP-43, caveolin-1, NCAM, hippocampal neuron counts and Y-maze correct response rate, decreased Bax, cleaved caspase-3, IL-1β, IL-2 and neuronal apoptosis on days 1 and 3 post-administration, reduced escape latency on days 1, 3, 5 and 7 (p<0.05) and diminished neuropathological damage in the hippocampal CA1 area. Conclusion: Administering low doses of ketamine can mitigate cognitive dysfunction induced by propofol anesthesia, enhance learning and memory capabilities, inhibit neuronal apoptosis, reduce inflammatory response and alter synaptic plasticity in rats. Its mechanism of action is linked to the activation of the PI3K/Akt signaling pathway.

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